Clotrimazole Lozenges

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
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1 DEFINITION

Clotrimazole Lozenges contain NLT 90.0% and NMT 110.0% of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) in a suitable molded base.

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Buffer: 0.3 g/L of anhydrous monobasic sodium phosphate and 0.35 g/L of anhydrous dibasic sodium phosphate in water. The resulting solution has a pH of 6.6-7.0.

Mobile phase: Acetonitrile and Buffer (1:1)

Diluent: Acetonitrile and water (1:1)

Standard solution: 0.2 mg/mL of USP Clotrimazole RS in Diluent

Sample solution: Nominally 0.2 mg/mL of clotrimazole in Diluent prepared as follows. Transfer a portion of powdered Lozenges (from NLT 20 Lozenges) equivalent to 5 mg of clotrimazole to a 25-mL volumetric flask. Dilute with Diluent to volume. Sonicate for about 10 min, and centrifuge at 3500 rpm for about 15 min at ambient temperature to obtain a clear supernatant. Use the clear supernatant for injection.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 206 nm. For Identification test B use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing L85

Flow rate: 1 mL/min

Injection volume: 8 µL

Run time: 1.25 times the retention time of clotrimazole

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) in the portion of Lozenges taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clotrimazole from the Sample solution

r_s = peak response of clotrimazole from the Standard solution

C_s = concentration of USP Clotrimazole RS in the Standard solution (mg/mL)

C_u = nominal concentration of clotrimazole in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711).

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 45 min

Determine the amount of clotrimazole (C₂₂H₁₇CIN₂) dissolved by using the following method.

Buffer A: 4.4 mg/mL of dibasic potassium phosphate in water

Buffer B: 17.4 mg/mL of dibasic potassium phosphate in water

Mobile phase: Methanol and Buffer A (4:1)

Diluent: Methanol and Buffer B (60:40)

Standard stock solution: 0.02 mg/mL of USP Clotrimazole RS in Medium

Standard solution: 4 µg/mL from the Standard stock solution in Diluent

Sample solution: Withdraw 25 mL of the solution under test from the vessel. Pass through a polyvinylidene difluoride filter of 0.45-µm pore size, and discard the first 10 mL of the filtrate. Transfer 5.0 mL of filtrate to a 25-mL volumetric flask, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 3.9-mm x 7.5-cm; packing L1

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) dissolved:

Result = (r_u/r_s) × (C_s/L) x D x V x 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution s

C_s = concentration of the Standard solution (mg/mL)

L = label claim of clotrimazole (mg/Lozenge)

D = dilution factor for the Sample solution, 5

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of clotrimazole (C₂₂H₁₇CIN₂) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Buffer, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1 µg/mL each of USP Clotrimazole RS, USP Clotrimazole Related Compound A RS, and USP Imidazole RS in Diluent

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 4.0 between clotrimazole related compound A and imidazole peaks; NLT 4.0 between clotrimazole and clotrimazole related compound A peaks

Relative standard deviation: NMT 2.0% for clotrimazole, clotrimazole related compound A, and imidazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity in the portion of Lozenges taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of the corresponding specified impurity from the Sample solution

r_s = peak response of the corresponding specified impurity from the Standard solution s

C_s = concentration of the corresponding USP Reference Standard in the Standard solution (mg/mL)

C_u = nominal concentration of clotrimazole in the Sample solution (mg/mL)

Calculate the percentage of any unspecified impurity in the portion of Lozenges taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of any unspecified impurity from the Sample solution

r_s = peak response of clotrimazole from the Standard solution s

C_{s =} concentration of USP Clotrimazole RS in the Standard solution (mg/mL)

C_u = nominal concentration of clotrimazole in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard any impurity peak less than 0.05%.

Table 1

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE: Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Clotrimazole RS

USP Clotrimazole Related Compound A RS

(o-Chlorophenyl) diphenylmethanol.

C₁₉H₁₅CIO 294.78

USP Imidazole RS